Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
6142725 | Virus Research | 2013 | 10 Pages |
Abstract
Viral expression varies widely between untransformed HTLV-1 positive clones derived from infected individuals without malignancy. Here we show that, in the absence of malignancy, 68% of HTLV-1 positive clones carry deleted (10%) or methylated (58%) 5â² LTR. These changes were found to contribute to the fluctuation of viral expression between clones. 5â² LTR deletions strongly impaired tax expression and thereby clonal expansion, telomere homeostasis, and genetic instability. The effects of CpG methylation on viral transcription were qualitatively and quantitatively different from those of LTR deletions and preserved the preleukemic features of HTLV-1+CD4+ clones. 5â² LTR methylation varied not only between clones but also between cells belonging to the same clones, between distinct integrated sequences within the same cells, and between CpG dyads along the 5â² LTR. Such distributions suggest that a dynamic methylation spectrum might help sustain persistent infection.
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Authors
David Sibon, Linda Zane, Manale El Idrissi, Marie-Hélène Delfau-Larue, Antoine Gessain, Olivier Gout, Franck Mortreux, Eric Wattel,